The medicinal uses of the genus Bletilla in traditional Chinese medicine: A phytochemical and pharmacological review.

Taxifolin attenuates neuroinflammation and microglial pyroptosis via the PI3K/Akt signaling pathway after spinal cord injury.

Stilbenes are polyphenolic allelochemicals synthesized by plants, especially grapes, peanuts, rhubarb, berries, etc., to defend themselves under stressful conditions. They are now exploited in medicine for their antioxidant, anti-proliferative and anti-inflammatory properties. Inflammation is the immune system's response to invading bacteria, toxic chemicals or even nutrient-deprived conditions. It is characterized by the release of cytokines which can wreak havoc on healthy tissues, worsening the disease condition. Stilbenes modulate NF-κB, MAPK and JAK/STAT pathways, and reduce the transcription of inflammatory factors which result in maintenance of homeostatic conditions. Resveratrol, the most studied stilbene, lowers the Michaelis constant of SIRT1, and occupies the substrate binding pocket. Gigantol interferes with the complement system. Besides these, oxyresveratrol, pterostilbene, polydatin, viniferins, etc., are front runners as drug candidates due to their diverse effects from different functional groups that affect bioavailability and molecular interactions. However, they each have different thresholds for toxicity to various cells of the human body, and thus a careful review of their properties must be conducted. In animal models of autoinflammatory diseases, the mode of application of stilbenes is important to their absorption and curative effects, as seen with topical and microemulsion gel methods. This review covers the diversity seen among stilbenes in the plant kingdom and their mechanism of action on the different inflammatory pathways. In detail, macrophages' contribution to inflamed conditions in the liver, the cardiac, connective and neural tissues, in the nephrons, intestine, lungs and in myriad other body cells is explored, along with detailed explanation on how stilbenes alleviate the symptoms specific to body site. A section on the bioavailability of stilbenes is included for understanding the limitations of the natural compounds as directly used drugs due to their rapid metabolism. Current delivery mechanisms include sulphonamides, or using specially designed synthetic drugs. It is hoped that further research may be fueled by this comprehensive work that makes a compelling argument for the exploitation of these compounds in medicine. 

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Stilbenes, a Versatile Class of Natural Metabolites for Inflammation—An Overview

Stilbenes are a large class of plant secondary metabolites belonging to the wider family of natural polyphenols, which are widely distributed in food and medicinal plants. Stilbenes exist as in plant monomers or polymers, and their structural complexities and diversities increase due to their polymerization. In recent years, stilbenes have been paid extensive attention as active molecules of functional foods and natural medicines. So far, 1041 stilbenes have been isolated from the plant, which were mainly found in plant families of Dipterocarpaceae, Moraceae, Gnetaceae, Orchidaceae, Polygonaceae, Euphorbiaceae, Stemonaceae, Cyperaceae, Vitaceae and Asparagaceae, et al. Among them, 483 natural oligostilbenes have been reported, of which 284 compounds were identified from families of Dipterocarpaceae and Gnetaceae, accounting for 58% of the total. Stilbenes possessed a variety of biological activities including antioxidant, anti-cancer, anti-inflammatory, anti-bacterial and anti-HIV, especially the anti-cancer and antioxidant activities. For instance, resveratrol, which is widely present in more than 70 plant species, including grapes, berries and peanuts, plays a prominent role in the prevention and treatment of neurodegenerative diseases, diabetes and cancer. In addition, resveratrol is also a functional active molecule of red wine, which can reduce the damage of oxidative stress to the cardiovascular system by neutralizing free oxygen radicals and reactive nitrogenous radicals. This article summarizes and analyzes the research progress of the structures and pharmacological activities of stilbenes and their derivatives. According to their distributions, structural classifications and pharmacological activities, these compounds were systematically reviewed, which provided the basis for the further development and utilization of them. 

Bioactive stilbenes from plants

Bletilla striata has been used for thousands of years and shows the functions of stopping bleeding, reducing swelling, and promoting healing in traditional applications. For Bletilla striata, Bletilla striata polysaccharides (BSP) is the main active ingredient, exhibiting biological functions of anti-inflammatory, anti-oxidant, anti-fibrotic, immune modulation, anti-glycation, and so on. In addition, BSP has exhibited the characteristics of excipient such as bio-adhesion, bio-degradability, and bio-safety and has been prepared into a series of preparations such as nanoparticles, microspheres, microneedles, hydrogels, etc. BSP, as both a drug and an excipient, has already aroused more and more attention. In this review, publications in recent years related to the extraction and identification, biological activities, and excipient application of BSP are reviewed. Specifically, we focused on the advances in the application of BSP as a formulation excipient. We hold opinion that BSP not only needed more researches in the mechanisms, but also the development into hydrogels, nano-formulations, tissue engineering, and so on. And we believe that this paper provides a beneficial reference for further BSP innovation and in-depth research and promotes the use of these natural products in pharmaceutical applications. 

Dual properties of pharmacological activities and preparation excipient: Bletilla striata polysaccharides.

Stilbenes from the tubers of Bletilla striata with potential anti-neuroinflammatory activity.

Background: Alzheimer’s disease (AD) as an age-related, irreversible neurodegenerative disease, characterized by cognitive dysfunction, has become progressively serious with a global rise in life expectancy. As the failure of drug elaboration, considerable research effort has been devoted to developing therapeutic strategies for treating AD. TCM is gaining attention as a potential treatment for AD. Gastrodia elata Blume, Polygala tenuifolia Willd., Cistanche deserticola Ma, Rehmannia lutinosa (Gaertn.)DC., Acorus gramineus Aiton, and Curcuma longa L. (GPCRAC) are all well-known Chinese herbs with neuroprotective benefits and are widely used in traditional Chinese decoction for AD therapy. However, the efficacy and further mechanisms of GPCRAC extracts in AD experimental models are still unclear. The purpose of this study was to investigate the synergistic protective efficacy of GPCRAC extracts (composed of extracts from these six Chinese medicines), and the protein targets mediated by GPCRAC extracts in treating AD. Methods: Scopolamine-induced cognitive impairment mouse model was established to determine the neuroprotective effects of GPCRAC extracts in vivo, as shown by behavioral tests and cerebral cholinergic function assays. To identify the potential molecular mechanism of GPCRAC extracts against AD, label-free quantitative proteomics coupled with tandem mass spectrometry (LC-MS/MS) were performed. The integrated bioinformatics analysis was applied to screen the core differentially expressed proteins in vital canonical pathways. Critical altered proteins were validated by qPCR and Western blotting. Results: Administration of GPCRAC extracts significantly recovered scopolamine-induced cognitive impairment, as evidenced by the improved learning and memory ability, increased Ach content and ChAT activity, as well as decreased AchE activity in the hippocampus of mice. In total, 390 proteins with fold-change>1.2 or <0.83 and p < 0.05 were identified as significant differentially expressed proteins, of which 110 were significantly up-regulated and 25 were significantly down-regulated between control and model group. By mapping the significantly regulated proteins, we identified five hub proteins: PPP2CA, Gsk3β, PP3CC, PRKACA, and BCL-2 that were associated with dopaminergic synapse and apoptosis signaling pathway, respectively. Western blotting and QPCR demonstrate that the expression levels of these core proteins could be significantly improved by the administration of GPCRAC extracts. These pathways and some of the identified proteins are implicated in AD pathogenesis. Conclusion: Administration of GPCRAC extracts was effective on alleviating scopolamine-induced cognitive impairment, which might be through modulation of dopaminergic synapse and apoptosis signaling pathway. Consequently, our quantitative proteome data obtained from scopolamine-treated model mice successfully characterized AD-related biological alterations and proposed novel protein biomarkers for AD.

Chinese Herbal Extracts Exert Neuroprotective Effect in Alzheimer’s Disease Mouse Through the Dopaminergic Synapse/Apoptosis Signaling Pathway

Natural therapeutic agents for neurodegenerative diseases from the shells of Xanthoceras sorbifolium.

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Stilbenes from the tubers of Bletilla striata with potential anti-neuroinflammatory activity.

Chinese Herbal Extracts Exert Neuroprotective Effect in Alzheimer’s Disease Mouse Through the Dopaminergic Synapse/Apoptosis Signaling Pathway

Natural therapeutic agents for neurodegenerative diseases from the shells of Xanthoceras sorbifolium.